As a Visiting Scientist at the National Center for Human Genome Research, NIH, I have established an integrated Fluorescent sequencing facility to rapidly sequence cDNA involved in Genetic lesions such as Trinucleotide repeat expansions. This system includes automated analysis of sequence data and it's presentation in a HTML based browsing system on the World Wide Web. We are continuing to develop the Genomic Walking sequencing technology to the detection of hypermethylation events in human disease states such as Prader-Willi/Angelman syndrome and Prostate cancer. In this context, we have made significant progress in the use of an ultra-sensitive Multiphoton detection system to directly sequence human genomic DNA. We have also implemented the bisulfite chemistry based method to indirectly detect hypermethylation events. We have characterized a highly conserved Line Element and have indications that this element may rearrange during development. We will investigate the distribution of the element in various tissues using FISH technology as well as sequence copies of the repeat to fully characterize it's distribution and function. We are developing new technology to detect SSCP and micro-satellite markers to increase the throughput and sensitivity of the methods. These detection techniques include the a novel Mass Spectroscopy technology, a new HPLC column matrix and the ultra-sensitive Multiphoton Detection system. We are developing informatics tools to assist in the reconstruction of metabolic pathways from DNA sequence data and the subsequent modeling of the metabolic flux through the network. It is hoped that this line of research will facilitate the elucidation of complex metabolic disorders.